caa a22 4500 477125697 CHVBK 20180405111648.0 cr unu---uuuuu 170330e19970601xx s 000 0 eng 10.1023/A:1012190120061 doi (NATIONALLICENCE)springer-10.1023/A:1012190120061 The Effect of Benzyl Alcohol on Recombinant Human Interferon-γ [Elektronische Daten] [Xanthe Lam, Thomas Patapoff, Tue Nguyen] Purpose. The goal of this study was to investigate the conformational change and aggregation of recombinant human interferon-gamma (rhIFN-γ) as a result of interaction between benzyl alcohol and the protein. The effects of buffer concentration, buffer species, ionic strength, rhIFN-γ and benzyl alcohol concentrations on the dynamics of the interaction in liquid formulations were also examined. Methods. The effect of benzyl alcohol on the secondary and tertiary structure of rhIFN-γ in succinate and acetate buffers was studied using far-UV and near-UV circular dichroism spectrophotometry, respectively. Dynamic light scattering was employed to detect aggregate formation due to the interaction of benzyl alcohol with rhIFN-γ. Results. The addition of benzyl alcohol at 0.9% (w/v) in various liquid rhIFN-γ formulations induced changes in circular dichroism (CD) spectra of the protein in the near-UV region, while the CD spectra in the far-UV region remained unaltered. There were gradual decreases in ellipticity with time throughout the near-UV CD spectra. The decreases in near-UV ellipticity induced by benzyl alcohol were accompanied by the formation of high molecular weight aggregates as measured by dynamic light scattering. Loss in near-UV ellipticity was accelerated at lower protein concentration and by increasing buffer or benzyl alcohol concentration. It was also faster in succinate than in acetate buffer. Formulation ionic strength did not affect the CD spectral changes in both the near- and far-UV regions. Conclusions. Interaction between benzyl alcohol and rhIFN-γ is formulation dependent. Protein concentration, buffer species, buffer concentration, and preservative concentration play a significant role in determining the extent of the interaction and consequently the stability of the product. Plenum Publishing Corporation, 1997 recombinant human interferon-γ (rhIFN-γ) nationallicence benzyl alcohol nationallicence circular dichroism nationallicence ellipticity nationallicence dynamic light scattering nationallicence aggregation nationallicence Lam Xanthe Department of Pharmaceutical Research and Development, Genentech, Inc., 460 Pt. San Bruno Blvd., South San Francisco, California, 94080 aut Patapoff Thomas Department of Pharmaceutical Research and Development, Genentech, Inc., 460 Pt. San Bruno Blvd., South San Francisco, California, 94080 aut Nguyen Tue Department of Pharmaceutical Research and Development, Genentech, Inc., 460 Pt. San Bruno Blvd., South San Francisco, California, 94080 aut Pharmaceutical Research Kluwer Academic Publishers-Plenum Publishers 14/6(1997-06-01), 725-729 0724-8741 14:6<725 1997 14 11095 https://doi.org/10.1023/A:1012190120061 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1023/A:1012190120061 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Lam Xanthe Department of Pharmaceutical Research and Development, Genentech, Inc., 460 Pt. San Bruno Blvd., South San Francisco, California, 94080 aut NATIONALLICENCE 700 1- Patapoff Thomas Department of Pharmaceutical Research and Development, Genentech, Inc., 460 Pt. San Bruno Blvd., South San Francisco, California, 94080 aut NATIONALLICENCE 700 1- Nguyen Tue Department of Pharmaceutical Research and Development, Genentech, Inc., 460 Pt. San Bruno Blvd., South San Francisco, California, 94080 aut NATIONALLICENCE 773 0- Pharmaceutical Research Kluwer Academic Publishers-Plenum Publishers 14/6(1997-06-01), 725-729 0724-8741 14:6<725 1997 14 11095 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer